mirvetuximab soravtansine-gynx — Drug Monograph

Mirvetuximab Soravtansine (Elahere) — Folate Receptor Alpha ADC Overview

Mirvetuximab soravtansine (Elahere) is a folate receptor alpha (FRα)-directed antibody-drug conjugate (ADC) for FRα-high, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Its anti-FRα antibody delivers the maytansinoid DM4 payload, which disrupts microtubules to induce mitotic arrest and apoptosis. FRα-high status (≥75% of tumor cells staining ≥2+ by the Ventana FOLR1 assay) is required before treatment. This monograph covers mirvetuximab soravtansine dosing (6 mg/kg adjusted ideal body weight IV every 3 weeks), the FRα ADC mechanism, platinum-resistant ovarian cancer indications, FRα IHC biomarker thresholds, and proactive management of keratopathy and ocular toxicities.

Indications (FDA / NCCN)

• FRα-high, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after 1–3 prior regimens (MIRASOL)
• First ADC to show an OS benefit in platinum-resistant ovarian cancer
• FRα-high (≥75% of cells ≥2+) confirmed by the Ventana FOLR1 RxDx assay before starting

Dosing

• Standard dose: 6 mg/kg adjusted ideal body weight (AIBW) IV every 3 weeks
• Dose reductions: 5 mg/kg → 4 mg/kg AIBW; discontinue if 4 mg/kg not tolerated
• Premedicate: dexamethasone 8 mg IV, antihistamine, and H2 blocker
• AIBW dosing reduces exposure variability (IBW uses the female formula)

Monitoring

• Ophthalmic exam (visual acuity + slit-lamp) before starting and before each cycle
• Mandatory ocular prophylaxis: topical corticosteroid drops + preservative-free lubricants
• Avoid contact lenses during treatment
• Peripheral neuropathy assessment each cycle

Brand names: Elahere

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-FRα (folate receptor alpha) monoclonal antibody conjugated to the maytansinoid DM4 via a cleavable disulfide linker (DAR ~3.4). Upon internalization, DM4 is released, binds tubulin, and inhibits microtubule polymerization, inducing mitotic arrest and apoptosis.

FDA Indications

• FRα-positive (high expression by Ventana FOLR1 RxDx assay), platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who received 1–3 prior systemic treatment regimens (accelerated approval November 2022; regular approval based on MIRASOL confirming OS benefit: median OS 16.46 vs 12.75 months vs investigator-choice chemotherapy)

Common Side Effects

• Blurred vision
• Keratopathy / superficial punctate keratitis
• Dry eye
• Nausea
• Fatigue
• Peripheral neuropathy
• Diarrhea
• Decreased appetite
• Alopecia

Clinical Pearl

MIRASOL (ASCO 2023) was the first ADC trial to demonstrate an overall survival advantage in platinum-resistant ovarian cancer (HR 0.67). FRα-high status (≥75% of tumor cells staining ≥2+) is required; ~35–40% of platinum-resistant ovarian cancers qualify. Ocular toxicity is the key dose-limiting adverse effect and almost entirely manageable with the mandatory prophylaxis regimen.

Related Therapies & Mechanisms

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